Sodium Cyanide → 4-Fluoro-2-iodophenylacetic acid

To the benzylic bromide 322 (4.90 g, 15.6 mmol) in ethanol (50 mL) was added sodium cyanide (1. 60 g, 32.6 mmol) in water (10 mL) and the mixture was heated to reflux for 3 h. It was then concentrated, partitioned between diethyl ether and water; organic phase was collected, washed with brine, dried (MgSO4), filtered and concentrated to afford crude nitrile 323. To this material in 1:1 THF/methanol (50 mL) was added lithium hydroxide monohydrate (1.75 g, 41.7 mmol), in water (12 mL) and the mixture was heated to reflux for 24 h. It was then cooled, partially concentrated and the aqueous residue was washed with ether, then acidified with 3M HCl (aq) and extracted with ether. The extract was washed with brine, dried (MgSO4), filtered and concentrated to yield acid 324 (3.95 g, 90% yield over two steps). LCMS: (M+Na) 303.0.

1. temperaturethe mixture was heated
2. temperatureto reflux for 3 h
3. concentrationIt was then concentrated
4. custompartitioned between diethyl ether and water
5. customorganic phase was collected
6. washwashed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford crude nitrile 323
11. temperatureto reflux for 24 h
12. temperatureIt was then cooled
13. concentrationpartially concentrated
14. washthe aqueous residue was washed with ether
15. extractionextracted with ether
16. washThe extract was washed with brine
17. dry with materialdried (MgSO4)
18. filtrationfiltered
19. concentrationconcentrated

ORD record

ord-f1c15cd52e524c899e820c3d0a1f2954

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07790729B2